US4613665A - Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained - Google Patents

Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained Download PDF

Info

Publication number
US4613665A
US4613665A US06/464,996 US46499683A US4613665A US 4613665 A US4613665 A US 4613665A US 46499683 A US46499683 A US 46499683A US 4613665 A US4613665 A US 4613665A
Authority
US
United States
Prior art keywords
group
substance
heparin
substrate
amino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US06/464,996
Other languages
English (en)
Inventor
Olle Larm
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Application granted granted Critical
Publication of US4613665A publication Critical patent/US4613665A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005—Use of materials characterised by their function or physical properties
    • A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005—Use of materials characterised by their function or physical properties
    • A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • A61L33/0029—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate using an intermediate layer of polymer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/06—Use of macromolecular materials
    • A61L33/08—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/3085—Chemical treatments not covered by groups B01J20/3007 - B01J20/3078
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3206—Organic carriers, supports or substrates
    • B01J20/3208—Polymeric carriers, supports or substrates
    • B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3206—Organic carriers, supports or substrates
    • B01J20/3208—Polymeric carriers, supports or substrates
    • B01J20/3212—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
    • B01J20/3217—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • B01J20/3268—Macromolecular compounds
    • B01J20/3272—Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • B01J20/3268—Macromolecular compounds
    • B01J20/3272—Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
    • B01J20/3274—Proteins, nucleic acids, polysaccharides, antibodies or antigens
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3289—Coatings involving more than one layer of same or different nature
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
    • B01J2220/58—Use in a single column
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
    • B01J2220/64—In a syringe, pipette, e.g. tip or in a tube, e.g. test-tube or u-shape tube

Definitions

  • the present invention relates to a new process to produce by covalent binding conjugates of a substance containing a 2-amino-2-deoxyglycopyranosyl unit and a substrate containing primary amino groups.
  • Such substrates can be constituted by plastic surfaces, for example for binding heparin to medical instruments to provide for anti-coagulation effect, they may be proteins, for example for preparing neoglycoproteins (synthetic glycoproteins) for cell stimulation, preparation of antigenic determinants etc., or they can be constituted by for example gels for affinity chromatography.
  • proteins for example for preparing neoglycoproteins (synthetic glycoproteins) for cell stimulation, preparation of antigenic determinants etc.
  • they can be constituted by for example gels for affinity chromatography.
  • the binding can be provided with a high degree of specificity.
  • the biological activity of the substance to be coupled to the substrate and the properties of the latter shall not be considerably changed.
  • the present invention relates to coupling of organic substances to substrates of different types, the common denominator of the substrates being the fact that they contain primary amino groups.
  • the invention will be exemplified mainly with reference to polysaccharides, particularly those possessing biological activity, but it should be observed that this exemplification only is intended to be illustrative and not limiting.
  • Heparin is built up from alternating glycuronic acid and glucosamine units.
  • the glycuronic acid units consist of D-glycuronic acid and L-iduronic acid. These are respectively ⁇ - and ⁇ -(1,4)-bound to the D-glucosamine units.
  • a large proportion of the L-iduronic acid residues are sulfated in the 2-position.
  • the D-glucosamine units are N-sulfated, sulfated in the 6-position and are ⁇ -(1,4)-bound to the uronic acid residues.
  • Certain D-glucosamine units are also sulfated in the 3-position.
  • Hyaluronic acid (ref. 2)
  • Hyaluronic acid is composed of alternating 1,4-bound ⁇ -D-glucuronic acid and 1,3-bound N-acetyl- ⁇ -D-glucosamine units.
  • Dermatan sulfate is composed of alternating L-iduronic acid and N-acetyl-D-galactosamine units which are respectively ⁇ -(1,3)- and ⁇ -(1,4)-bound.
  • the polysaccharide is partially O-sulfated.
  • Chitosan is built up from ⁇ -(1,4)-bound D-glucosamine residues.
  • Heparin imparts its blood-anticoagulating effect by activating the plasma protein antithrombin (AT) (ref. 4).
  • AT plasma protein antithrombin
  • Activated AT inhibits a number of serine proteases in blood (factor X (X a ) thrombine . . . ).
  • antithrombin is isolated from blood plasma by affinity chromatography on heparin-Sepharoses (ref. 5).
  • the methods heretofore used to bind heparin to gels have, however, resulted in the heparin losing a significant part of its activity.
  • Heparin which simply can be described as a polymer anionic compound, easily forms water-insoluble ion complexes with cation compounds, a fact which has been used for the production of surface-bound ion complexes of heparin, (ref. 7).
  • a decisive disadvantage of such processes is, however, the fact that ion complexes with heparin are unstable when contacting the blood in view of which the effect will be of short duration.
  • In order to avoid rapid dissolution one has tried different methods of binding heparin with stable covalent bonds. The attempts made up to now along this route have not led to the desired result but as a rule the biological activity of the heparin has been lost.
  • a third method consists in first preparing a surface-bound ion complex, see Canadian Pat. No. 948,105, which is then stabilized by chemical reduction with glutar dialdehyde.
  • a heparin surface prepared by the last-mentioned method has verified non-trombogenic properties. However, a small quantity of heparin will be released during an initial phase when contacting blood.
  • the implants can acquire better tissue affinity. In this manner one avoids complementary activation and activation of the mono-nuclear cell system which is part of the defense of the body against external attack.
  • the present invention enables effective and easy coupling of hyaluronic acid to solid materials, such as plastics and metals.
  • polysaccharides can be linked to a surface in two different ways which are illustrated in the appended FIG. 1 with FIGS. A and B.
  • the present invention has thus for its object to provide a process for covalent binding of oligomeric or polymeric organic substances to substrates of different types containing primary amino groups.
  • the invention relates in particular to a new technique for coupling oligo or polysaccharides to substrates.
  • the process of the present invention is characterized thereby that the substance to be coupled is subjected to degradation by diazotation to form a substance fragment having a free terminal aldehyde group.
  • the substance fragment is then brought to react through its aldehydo group with the amino group of the substrate to form a Schiffs' base which then by reduction is converted to a secondary amine.
  • the substance to be coupled to the substrate contains a 2-amino-2-deoxyglycopyranosyl residue the NH 2 -function of which in the most stable conformation is equatorially oriented.
  • this entity is diazotized and converted to a terminal 1-deoxy-2,5-anhydrohexitol entity.
  • the diazotizing reaction can be illustrated with the reaction equation according to FIG. 2 on the appended drawing.
  • the substance is thus partially degraded and a reactive aldehyde group is provided at the reducing end.
  • the formed substance fragment with the terminal aldehyde group is then reacted with a substrate containing primary amino groups.
  • the reaction can take place in water at pH 3-7 or within the same pH-range in a suitable organic solvent, for example formamide or dimethyl sulphoxide.
  • a suitable organic solvent for example formamide or dimethyl sulphoxide.
  • a suitable reducing agent for example a cyanoborohydride, preferably of an alkali metal, such as sodium, potassium or lithium, converted to form stable secondary amines. (Ref. 8).
  • the diazotation is suitably performed in an aqueous solution with a suitable diazotizing agent, for example a nitrite, such as sodium nitrite, in acid solution or butyl nitrite. While the invention is not limited to any particular theory it is assumed that the diazotation is provided by the formation of NO + -ions, in view of which the diazotation is thus suitably performed with an agent capable of forming such ions.
  • a suitable diazotizing agent for example a nitrite, such as sodium nitrite, in acid solution or butyl nitrite.
  • oligo or polysaccharides containing glucosamine or galactosamine entities there may be mentioned oligo or polysaccharides containing glucosamine or galactosamine entities.
  • Said substances are preferably selected from heparin and heparin derivatives, at least partially deacetylated dermatan sulfate, chitosan and at least partially deacetylated hyaluronic acid.
  • plastic surfaces containing primary amino groups for example plastic objects to which it is desirable to impart a non-thrombogenic surface, aminated gels and proteins.
  • a conjugate formed from the said substance and a substrate.
  • This conjugate consists of an 1-deoxy-2,5-anhydrohexitol entity which constitutes a terminal entity in a polysaccharide and which in the 1-position is covalently bound to an amino group associated with the substrate.
  • the hexitol entity contained in the conjugate is preferably a mannitol entity.
  • the polysaccharide is preferably derived from heparin, hyaluronic acid or from chitosan.
  • the hexitol entity is a talitol entity, the polysaccharide being derived from for example dermatan sulfate.
  • a solution of 100 mg of the polysaccharide in 30 ml of water is cooled to 2° C.
  • the solution is allowed to pass a 1.6 ⁇ 7 cm column with Dowex 50-8X (H + ) (200-400 mesh) at a rate of 2 ml/min.
  • the column is washed with 20 ml water.
  • To the eluate there is added 50 ml peroxide-free 1,3-dimethoxy ethane and 0.01 ml 1-butyl nitrite and the mixture is left at -20° C. for 24 hours.
  • the reaction mixture is worked up by dialysis against distilled water and lyophilization.
  • Tubings of polyethylene were initially provided with a negative surface charge (sulfate groups) by treatment for 2 minutes with concentrated sulphuric acid containing 2 g/l of KMnO 4 .
  • a negative surface charge sulfate groups
  • sulphuric acid containing 2 g/l of KMnO 4 .
  • a polymer cationic tenside Polymin SN; BASF
  • heparin diazotized as in Example 2 (20 mg/ml) (a) or 2 mg/ml (b) and sodium cyanoborohydride (0.5 mg/ml) in a phosphate buffer pH 7.0 for 24 hours at room temperature.
  • the heparinized surface was finally carefully rinsed with water.
  • Carbazol test (ref. 9) showed that ⁇ 10 ⁇ g heparin/cm 2 had been attached to the surface both in case a and in case b.
  • the quantity of heparin which is available for interaction with protein was semi-quantitatively analyzed in the following manner. The measurement is based on the fact that thrombin is bound to heparin whereafter the quantity of surface-bound thrombin is measured by reaction (hydrolysis) of a thrombin specific substrate, S-2238 (Kabi Diagnostica) the rate of conversion of which can be simply established by spectrophotometry.
  • Measurement of the quantity of surface-bound thrombin may be utilized also for testing the functional non-thrombogenic properties of the surface.
  • the heparin surface (test surface) is initially incubated with human citrate plasma for 40 minutes for the purpose of providing to the surface a relevant protein adsorbate.
  • the plasma is at the same time utilized to detect possible leakage of heparin.
  • the test surface is divided up into two groups. The first group is rinsed with only a physiologic saline, the other one also with defibrinogenated plasma (plasma freed from fibrinogen and thus non-coagulatable).
  • the criteria for a non-thrombogenic surface are that the thrombin uptake which is measured under the same conditions as indicated above is at least 0.5 un.ab. in group I and less than 0.05 un.ab. in group II.
  • the positive test result shows that the heparin surface by interaction with plasma proteins has the capacity of inhibiting thrombin, i.e. the surface shows biological activity.
  • Measurement of heparin activity in the plasma rotating in the test tubings showed that less than 0.002 Iu heparin/cm 2 had been released from the surface, which is within the margin of error for this method.
  • heparin surfaces were tested with regard to adhesion of thrombocytes.
  • Tubings were rotated with fresh human citrate blood for 20 minutes and were then rinsed in a standardized manner with saline.
  • ATP adenosine triphosphate
  • the test showed that the thrombocyte adhesion is strongly reduced compared to the corresponding untreated surface.
  • Tubings of polyethylene were aminated by adsorption of polymer cation tenside, Polymin SN® (BASF), in two different ways.
  • PE-hoses were treated without preceding sulfatization with a borate buffer solution pH 9 containing 0.5% glutardialdehyde and 0.0005% Polymin for five minutes at room temperature. After rinsing with water the tubings were incubated with an aqueous solution of dextran sulfate (Pharmacia Fine Chemicals) (1 mg/ml, 0.15M NaCl, 50° C., 5 min. pH 3.0) and were then carefully rinsed with water. The result of this treatment is that the surface is provided with negative charge. Finally, the tubings were incubated for five minutes with a 0.1% aqueous solution of Polymin at pH 9.0 and were carefully rinsed with water.
  • dextran sulfate Pharmacia Fine Chemicals
  • Tubings prepared according to a and b were then incubated for two hours at 55° C. with a phosphate buffer solution pH 3.9 containing 0.25 mg/ml of heparin diazotized as in Example 2 (mucous, Kabi Vitrum) and 0.025 mg/ml sodium cyanoborohydride. The treatment was terminated with careful water rinsing.
  • the test shows that both a and b have satisfactorily low thrombocyte adhesion.
  • PVC-tubing (Tygon S-50-HL Class VI having an inner diameter of 3 mm) was aminated for 24 hours in room temperature by treatment with a solution of 1.6-diaminohexane in ethanol (5 g/100 ml). The tubing was washed with (1) ethanol (1 l) and (2) (1 l) and was heparinized as in Example 3. The carbazol reaction (ref. 9) showed that ⁇ 3 ⁇ g heparin/cm 2 had been bound to the surface.
  • nitrite degraded heparin (mucous, Kabi Vitrum) (10 mg, M w 2800) is fractionated on an AT-Sepharose column (ref. 11).
  • the high-active fraction ( ⁇ 2 mg) was eluated from the column by increasing the ion strength (1M NaCl). Fragments together with NaBH 3 CN (5 mg) were added to AT (50 mg) in a molar proportion of 1.2:1 (heparin: AT) in 10 ml phosphate buffer (0.2M, pH 7.0). After 24 hours the mixture was concentrated to 2 ml and transferred onto a Sephadex G-100 (Pharmacia Fine Chemicals) column.
  • the protein fraction was purified on a heparin-Sepharose-column (Pharmacia Fine Chemicals) where non-reacted AT adheres.
  • the fraction not adhering to the column (5.5 mg) contained 1.7 moles of fragments per mole of AT and had 100% of maximum activity.
  • the activity sank to 85% in the presence of polybren; a reagent cleaving non-covalent AT-heparin complexes.
  • Hyaluronic acid 100 mg was dissolved in water (10 ml) and sodium hydroxide (4 g) was added. The solution was mixed with DMSO (50 ml) in a serum bottle, nitrogen gas was blown into the bottle which was then sealed. The mixture was heated on a water bath 100° C. and shaken at intervals. After 1 hour the mixture was poured into 50% acetic acid (15 ml) and was then dialyzed against (1) tap water and (2) distilled water. After lyophilization partially deacetylated polysaccharide (95 mg) was obtained.
  • Dermatan sulfate (1 g) containing 2-amino-2-deoxy-N-acetyl glucosamine entities (N-acetyl-D-galacto- and glucopyranosyl entities) was dissolved in 30 ml hydrazine containing hydrazine sulfate (1.5 g). The mixture was heated for 0.5 hour to 105° C. in an ampoule. Then, the reagent was removed by vapourization under low pressure. The polysaccharide was dialyzed against (1) 10% acetic acid (1 l, over night) and (2) distilled water (5 l, over night).
  • Dermatan sulfate 50 mg
  • (gift from Ulf Lindahl) deacetylated as in Example 9 and diazotized as in Example 2
  • 5 ml phosphate buffer 0.2M, pH 7.0
  • NaBH 3 CN 5 mg
  • Colouring with toluidineblue showed that dermatan sulfate had been bound to the tubing.
  • Hyaluronic acid (Healon®, Pharmacia AB) (50 mg) deacetylated as in Example 9 and nitrite-degraded as in Example 2, was allowed to react with a tubing as in Example 10, and colouring with acianblue showed that hyaluronic acid had been bound to the surface.
  • the quantity of surface-bound hyaluronic acid was analyzed with regard to surface-bound thrombin as in Examples 3 and 10.
  • Heparin (50 g), nitrite degraded as in Example 2 was dissolved in phosphate buffer 10 ml.
  • a solution of 1,6-diaminohexane (100 mg) in water (5 ml) was adjusted to pH 7.0 (0.5M HCl) and added together with NaBH 3 CN (10 mg) to the heparin solution.
  • the reaction mixture was dialyzed against (1) 10% acetic acid (2 l) and (2) distilled water (5 l). After concentration and lyophilization the coupling yield was analyzed with 1 H-NMR in DCl (ref. 10). Result: the heparin contains 7.5 percent by weight of 1,6-diaminohexane.
  • Dermatan sulfate 50 mg
  • N-deacetylated and nitrite-degraded as in Example 10 was coupled to 1,6-diaminohexane as in Example 12.
  • the mixture was worked up and analyzed as in Example 12. Result: the dermatan sulfate contained 1 percent by weight of 1,6-diaminohexane.
  • Chitosan (100 ml), N-deacetylated and nitrite-degraded as in Examples 9 and 10, respectively, was coupled to 1,6-diaminohexane as in Example 12. The mixture was worked up and analyzed as in Example 12. Result: The chitosan contained 0.5 percent by weight of 1,6-diaminohexane.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Surgery (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US06/464,996 1982-02-09 1983-02-08 Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained Expired - Lifetime US4613665A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8200751A SE8200751L (sv) 1982-02-09 1982-02-09 Forfarande for kovalent koppling for framstellning av konjugat och hervid erhallna produkter
SE8200751 1982-02-09

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US06873988 Division 1986-06-13

Publications (1)

Publication Number Publication Date
US4613665A true US4613665A (en) 1986-09-23

Family

ID=20345952

Family Applications (2)

Application Number Title Priority Date Filing Date
US06/464,996 Expired - Lifetime US4613665A (en) 1982-02-09 1983-02-08 Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained
US07/097,259 Expired - Lifetime US4810784A (en) 1982-02-09 1987-09-17 Process for covalent coupling for the production of conjugates, and products hereby obtained

Family Applications After (1)

Application Number Title Priority Date Filing Date
US07/097,259 Expired - Lifetime US4810784A (en) 1982-02-09 1987-09-17 Process for covalent coupling for the production of conjugates, and products hereby obtained

Country Status (7)

Country Link
US (2) US4613665A (enExample)
EP (1) EP0086186B1 (enExample)
JP (1) JPS58147404A (enExample)
AU (1) AU562784B2 (enExample)
CA (1) CA1227480A (enExample)
DE (1) DE3363568D1 (enExample)
SE (1) SE8200751L (enExample)

Cited By (157)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4745180A (en) * 1986-06-27 1988-05-17 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using heparin fragments
US4772419A (en) * 1985-03-01 1988-09-20 Pharmacia Ab Shaped article and processes for its preparation
US4810784A (en) * 1982-02-09 1989-03-07 Olle Larm Process for covalent coupling for the production of conjugates, and products hereby obtained
US4830852A (en) * 1984-12-20 1989-05-16 Merck & Co Inc. Covalently-modified neutral bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins and methods of preparing such polysaccharides and conjugates
US4851521A (en) * 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
US5001062A (en) * 1986-05-27 1991-03-19 Camurus Ab Antithrombogenic article containing lysozyme and heparin adsorbed on a substrate
US5100668A (en) * 1988-06-14 1992-03-31 Massachusetts Institute Of Technology Controlled release systems containing heparin and growth factors
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5202431A (en) * 1985-07-08 1993-04-13 Fidia, S.P.A. Partial esters of hyaluronic acid
US5213898A (en) * 1989-10-12 1993-05-25 Norsk Hydro A.S. Process for the preparation of surface modified solid substrates
US5262451A (en) * 1988-06-08 1993-11-16 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5292514A (en) * 1992-06-24 1994-03-08 Minnesota Mining And Manufacturing Company Azlactone-functional substrates, corneal prostheses, and manufacture and use thereof
US5310881A (en) * 1990-03-30 1994-05-10 Seikagaku Corporation Glycosaminoglycan-modified protein
US5338770A (en) * 1988-06-08 1994-08-16 Cardiopulmonics, Inc. Gas permeable thrombo-resistant coatings and methods of manufacture
US5342693A (en) * 1988-06-08 1994-08-30 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coating and methods of manufacture
US5344701A (en) * 1992-06-09 1994-09-06 Minnesota Mining And Manufacturing Company Porous supports having azlactone-functional surfaces
US5391580A (en) * 1992-03-20 1995-02-21 Anatrace Inc. Poly(sulfone-alpha-olefin) composite permselective membrane article for use in blood oxygenation
US5401410A (en) * 1992-06-12 1995-03-28 Gambro Dialysatoren Gmbh & Co. Kg Membrane and process for the production thereof
US5476665A (en) * 1994-04-13 1995-12-19 Minnesota Mining And Manufacturing Company Azlactone functional particles incorporated in a membrane formed by solvent phase inversion
US5529986A (en) * 1991-09-26 1996-06-25 Corline Systems Ab Conjugate, its preparation and use and a substrate prepared with the conjugate
US5532311A (en) * 1995-02-01 1996-07-02 Minnesota Mining And Manufacturing Company Process for modifying surfaces
US5541305A (en) * 1991-01-16 1996-07-30 Toyo Boseki Kabushiki Kaisha Composition compatible with blood
US5583213A (en) * 1995-05-12 1996-12-10 Minnesota Mining And Manufacturing Company Process to activate sulfated polysaccharides
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
WO1997007834A3 (en) * 1995-08-22 1997-03-27 Medtronic Inc Method for making heparinized biomaterials
US5672638A (en) * 1995-08-22 1997-09-30 Medtronic, Inc. Biocompatability for solid surfaces
US5696100A (en) * 1992-12-22 1997-12-09 Glycomed Incorporated Method for controlling O-desulfation of heparin and compositions produced thereby
US5700559A (en) * 1994-12-16 1997-12-23 Advanced Surface Technology Durable hydrophilic surface coatings
US5728420A (en) * 1996-08-09 1998-03-17 Medtronic, Inc. Oxidative method for attachment of glycoproteins to surfaces of medical devices
US5767108A (en) * 1995-08-22 1998-06-16 Medtronic, Inc. Method for making improved heparinized biomaterials
US5795875A (en) * 1994-05-06 1998-08-18 Glycomed Incorporated Therapeutic methods of using O-desulfated heparin derivatives
US5814407A (en) * 1994-10-28 1998-09-29 Societe Prolabo Glycosylated particle of latex or of inorganic oxide and process for the preparation thereof
US5821343A (en) * 1996-04-25 1998-10-13 Medtronic Inc Oxidative method for attachment of biomolecules to surfaces of medical devices
US5820917A (en) * 1995-06-07 1998-10-13 Medtronic, Inc. Blood-contacting medical device and method
US5837313A (en) * 1995-04-19 1998-11-17 Schneider (Usa) Inc Drug release stent coating process
US5843186A (en) * 1996-12-20 1998-12-01 Implemed, Inc. Intraocular lens with antimicrobial activity
US5879697A (en) * 1997-04-30 1999-03-09 Schneider Usa Inc Drug-releasing coatings for medical devices
US5891506A (en) * 1996-08-09 1999-04-06 Medtronic, Inc. Oxidative method for attachment of glycoproteins or glycopeptides to surfaces of medical devices
US5928916A (en) * 1996-04-25 1999-07-27 Medtronic, Inc. Ionic attachment of biomolecules with a guanidino moiety to medical device surfaces
US5945319A (en) * 1996-04-25 1999-08-31 Medtronic, Inc. Periodate oxidative method for attachment of biomolecules to medical device surfaces
US5972718A (en) * 1996-02-28 1999-10-26 The Blood Center Research Foundation Method of detecting heparin-induced thrombocytopenia
US5972717A (en) * 1995-05-10 1999-10-26 The Blood Center Research Foundation, Inc. Method and kit for detecting heparin induced thrombocytopenia
US5981710A (en) * 1997-07-21 1999-11-09 Baxter International, Inc. Therapeutic hemoglobin composition having isotropically increased size
US5980972A (en) * 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US6013099A (en) * 1998-04-29 2000-01-11 Medtronic, Inc. Medical device for delivering a water-insoluble therapeutic salt or substance
US6018035A (en) * 1997-07-21 2000-01-25 Baxter International Inc. Reagents for isotropic size enhancement of a peptide, protein, nucleotide or other substrate
US6033719A (en) * 1996-04-25 2000-03-07 Medtronic, Inc. Method for covalent attachment of biomolecules to surfaces of medical devices
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
RU2153877C2 (ru) * 1994-07-19 2000-08-10 Астра Актиеболаг Агент, стимулирующий регенерацию твердой ткани
US6106454A (en) * 1997-06-17 2000-08-22 Medtronic, Inc. Medical device for delivering localized radiation
RU2155592C2 (ru) * 1994-07-19 2000-09-10 Астра Актиеболаг Антиадгезионный агент
US6120536A (en) * 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US6146771A (en) * 1997-07-01 2000-11-14 Terumo Cardiovascular Systems Corporation Process for modifying surfaces using the reaction product of a water-insoluble polymer and a polyalkylene imine
US6197289B1 (en) 1997-07-01 2001-03-06 Terumo Cardiovascular Systems Corporation Removal of biologically active agents
US6203536B1 (en) 1997-06-17 2001-03-20 Medtronic, Inc. Medical device for delivering a therapeutic substance and method therefor
US6204254B1 (en) 1997-09-12 2001-03-20 Baxter International, Inc. Biocompatible surfaces and a method for their preparation
US6206914B1 (en) 1998-04-30 2001-03-27 Medtronic, Inc. Implantable system with drug-eluting cells for on-demand local drug delivery
WO2001037893A1 (en) * 1999-11-23 2001-05-31 Medicarb Ab Method of covalent coupling
US6309660B1 (en) 1999-07-28 2001-10-30 Edwards Lifesciences Corp. Universal biocompatible coating platform for medical devices
US6331422B1 (en) 1997-04-03 2001-12-18 California Institute Of Technology Enzyme-mediated modification of fibrin for tissue engineering
US6340465B1 (en) 1999-04-12 2002-01-22 Edwards Lifesciences Corp. Lubricious coatings for medical devices
US20020150585A1 (en) * 1997-10-03 2002-10-17 Galenica Pharmaceuticals, Inc. Use of imine-forming polysaccharides as adjuvants and immunostimulants
US20020165608A1 (en) * 2001-05-07 2002-11-07 Llanos Gerard H. Local drug delivery devices and methods for maintaining the drug coatings thereon
US6486140B2 (en) 1994-07-19 2002-11-26 Medicarb Ab Agents, and methods employing them, for the prevention or reduction of tissue adhesion at a wound site
US6491965B1 (en) 1995-11-30 2002-12-10 Hamilton Civic Hospitals Research Development, Inc. Medical device comprising glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US6562781B1 (en) 1995-11-30 2003-05-13 Hamilton Civic Hospitals Research Development Inc. Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US6573245B1 (en) 1998-04-28 2003-06-03 Galenica Pharmaceuticals, Inc. Modified polysaccharide adjuvant-protein antigen conjugates, the preparation thereof and the use thereof
US20030113812A1 (en) * 2001-10-02 2003-06-19 Hemperly John J. Proliferation and differentiation of stem cells using extracellular matrix and other molecules
US20030119186A1 (en) * 1998-08-27 2003-06-26 Eidgenossische Technische Hochschule Zurich Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides
US20030124705A1 (en) * 1995-11-30 2003-07-03 Berry Leslie Roy Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US20030161938A1 (en) * 2002-02-22 2003-08-28 Bo Johnson Composition and method for coating medical devices
US20030166833A1 (en) * 2001-12-18 2003-09-04 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20030187232A1 (en) * 1998-08-27 2003-10-02 Eidgenossische Technische Hochschule Zurich Universitat Zurich Growth factor modified protein matrices for tissue engineering
US6630460B2 (en) 2001-02-09 2003-10-07 Medtronic, Inc. Heparin compositions and methods of making and using the same
US20030195617A1 (en) * 1988-10-04 2003-10-16 Cordis Corporation Expandable intraluminal graft
US20040037886A1 (en) * 2002-08-26 2004-02-26 Li-Chien Hsu Drug eluting coatings for medical implants
US20040062882A1 (en) * 2002-09-30 2004-04-01 Andrea Liebmann-Vinson Cell adhesion resisting surfaces
US6723344B2 (en) 1999-04-22 2004-04-20 Eidgenossische Technische Hochschule Controlled release of non heparin-binding growth factors from heparin-containing matrices
US20040082513A1 (en) * 1997-04-03 2004-04-29 California Institute Of Technology Enzyme-mediated modification of fibrin for tissue engineering
US6776796B2 (en) 2000-05-12 2004-08-17 Cordis Corportation Antiinflammatory drug and delivery device
US20040213818A1 (en) * 2001-06-05 2004-10-28 Susumu Kashiwabara Antithrombotic compositions and medical instruments containing the same
US6894022B1 (en) 1998-08-27 2005-05-17 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20050152950A1 (en) * 1995-11-13 2005-07-14 Saffran Bruce N. Method and apparatus for macromolecular delivery using a coated membrane
EP1609494A1 (en) 2004-06-21 2005-12-28 Cordis Corporation Heparin barrier coating for controlled drug release
US6997949B2 (en) 1993-04-26 2006-02-14 Medtronic, Inc. Medical device for delivering a therapeutic agent and method of preparation
US20060088654A1 (en) * 1995-04-19 2006-04-27 Boston Scientific Scimed, Inc. Drug release coated stent
US7056550B2 (en) 2000-09-29 2006-06-06 Ethicon, Inc. - Usa Medical devices, drug coatings and methods for maintaining the drug coatings thereon
US20060148704A1 (en) * 2005-01-06 2006-07-06 Kuros Biosurgery Ag Supplemented matrices for the repair of bone fractures
US20060147443A1 (en) * 2004-12-22 2006-07-06 Kuros Biosurgery Ag Synthetic biomaterials having incorporated therein bioactive factors through enzymatically degradable linkages
US20060159650A1 (en) * 2005-01-14 2006-07-20 Bacterin, Inc. Composition and method for covalently coupling an antithrombotic substance and a hydrophilic polymer
US20060172438A1 (en) * 2004-10-04 2006-08-03 David Milunic Methods and kits for detecting heparin/platelet factor 4 antibodies
US7108701B2 (en) 2001-09-28 2006-09-19 Ethicon, Inc. Drug releasing anastomosis devices and methods for treating anastomotic sites
US20070010440A1 (en) * 2005-01-06 2007-01-11 Kuros Biosurgery Ag Local treatment of bone defects
US7195640B2 (en) 2001-09-25 2007-03-27 Cordis Corporation Coated medical devices for the treatment of vulnerable plaque
US20070087028A1 (en) * 1998-04-16 2007-04-19 Robert Falotico Intraluminal devices for the prevention and treatment of vascular disease
US7217286B2 (en) 1997-04-18 2007-05-15 Cordis Corporation Local delivery of rapamycin for treatment of proliferative sequelae associated with PTCA procedures, including delivery using a modified stent
US20070179597A1 (en) * 2000-09-29 2007-08-02 Davila Luis A Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US20070264301A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized biologically active entities having a high degree of biological activity following sterilization
US20070264302A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized biologically active entities having high biological activity following mechanical manipulation
US20070264308A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized Biologically Active Entities Having High Biological Activity Following Mechanical Manipulation
US7300662B2 (en) 2000-05-12 2007-11-27 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
US20070276476A1 (en) * 2000-09-29 2007-11-29 Llanos Gerard H Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US20080241349A1 (en) * 2007-04-02 2008-10-02 Ension, Inc. Process for preparing a substrate coated with a biomolecule
US20080253987A1 (en) * 2007-04-13 2008-10-16 Kuros Biosurgery Ag Polymeric tissue sealant
US20090169539A1 (en) * 2007-12-28 2009-07-02 Kuros Biosurgery Ag Pdgf fusion proteins incorporated into fibrin foams
US20090192079A1 (en) * 2007-10-09 2009-07-30 Genzyme Corporation Prolonged delivery of heparin-binding growth factors from heparin-derivatized collagen
US7625410B2 (en) 2001-05-02 2009-12-01 Boston Scientific Scimed, Inc. Stent device and method
US20100074938A1 (en) * 2008-09-15 2010-03-25 Stefan Oscarson Immobilised biological entities
US20100249689A1 (en) * 2007-06-18 2010-09-30 Exthera Medical Llc Device and method for restoration of the condition of blood
US20100272775A1 (en) * 2006-05-12 2010-10-28 Cleek Robert L Immobilized biologically active entities having a high degree of biological activity following sterilization
US20110064781A1 (en) * 2009-09-17 2011-03-17 Cleek Robert L Novel heparin entities and methods of use
WO2011110684A1 (en) 2010-03-12 2011-09-15 Carmeda Ab Immobilised biological entities
US8067022B2 (en) 1992-09-25 2011-11-29 Boston Scientific Scimed, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US8097642B2 (en) 1995-02-15 2012-01-17 Boston Scientific Scimed, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US8236048B2 (en) 2000-05-12 2012-08-07 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
WO2012123384A1 (en) 2011-03-11 2012-09-20 Gore Enterprise Holdings, Inc Improvements to immobilised biological entities
US8303609B2 (en) 2000-09-29 2012-11-06 Cordis Corporation Coated medical devices
US8409604B2 (en) 2006-05-12 2013-04-02 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity
US8480227B2 (en) 2010-07-30 2013-07-09 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US8575101B2 (en) 2005-01-06 2013-11-05 Kuros Biosurgery Ag Supplemented matrices for the repair of bone fractures
WO2014011813A1 (en) 2012-07-11 2014-01-16 Tissuetech, Inc. Compositions containing hc-ha/ptx3 complexes and methods of use thereof
US8685430B1 (en) 2006-07-14 2014-04-01 Abbott Cardiovascular Systems Inc. Tailored aliphatic polyesters for stent coatings
WO2014118382A1 (en) 2013-02-04 2014-08-07 W. L. Gore & Associates, Inc. Coating for substrate
US9005700B2 (en) 2011-10-12 2015-04-14 Novartis Ag Method for making UV-absorbing ophthalmic lenses
WO2015138862A1 (en) 2014-03-13 2015-09-17 W.L Gore & Associates, Inc. (Us) Implantable medical device
US9173989B2 (en) 2005-12-13 2015-11-03 Exthera Medical Corporation Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US9272075B2 (en) 2013-02-04 2016-03-01 W.L. Gore & Associates, Inc. Coating for substrate
US9408962B2 (en) 2009-12-01 2016-08-09 Exthera Medical Corporation Methods for removing cytokines from blood with surface immobilized polysaccharides
US9468706B2 (en) 2004-03-22 2016-10-18 Abbott Cardiovascular Systems Inc. Phosphoryl choline coating compositions
EP3095509A1 (en) 2015-05-18 2016-11-23 Defymed Membranes functionalized with heparin for bioartificial organs
US9669150B2 (en) 2007-06-18 2017-06-06 Exthera Medical Corporation Device and method for restoration of the condition of blood
US9693841B2 (en) 2007-04-02 2017-07-04 Ension, Inc. Surface treated staples, sutures and dental floss and methods of manufacturing the same
US9708087B2 (en) 2013-12-17 2017-07-18 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
EP3318294A1 (en) 2016-11-08 2018-05-09 Defymed Kit for in situ delivery of a compound of interest
US10338408B2 (en) 2012-12-17 2019-07-02 Novartis Ag Method for making improved UV-absorbing ophthalmic lenses
WO2019170859A2 (en) 2018-03-09 2019-09-12 Carmeda Ab Improvements to immobilising biological entities
WO2019170858A1 (en) 2018-03-09 2019-09-12 Carmeda Ab Improvements to processes for immobilising biological entities
US10449740B2 (en) 2015-12-15 2019-10-22 Novartis Ag Method for applying stable coating on silicone hydrogel contact lenses
US10457974B2 (en) 2013-11-08 2019-10-29 Exthera Medical Corporation Methods for diagnosing infectious diseases using adsorption media
US10537280B2 (en) 2011-02-15 2020-01-21 Exthera Medical Corporation Device and method for removal of blood-borne pathogens, toxins and inflammatory cytokines
US10589001B2 (en) 2011-03-16 2020-03-17 Kuros Biosurgery Ag Pharmaceutical formulation for use in spinal fusion
WO2020070258A1 (en) 2018-10-03 2020-04-09 Carmeda Ab Immobilised biological entities
US10639413B2 (en) 2013-06-24 2020-05-05 Exthera Medical Corporation Blood filtration system containing mannose coated substrate
US10786615B2 (en) 2016-03-02 2020-09-29 Exthera Medical Corporation Method for treating drug intoxication
US10830923B2 (en) 2017-12-13 2020-11-10 Alcon Inc. Method for producing MPS-compatible water gradient contact lenses
US10857283B2 (en) 2014-09-22 2020-12-08 Exthera Medical Corporation Wearable hemoperfusion device
US10940111B2 (en) 2014-06-15 2021-03-09 Yeda Research And Development Co. Ltd. Surface treatment by water-soluble polymers and lipids/liposomes
US11002884B2 (en) 2014-08-26 2021-05-11 Alcon Inc. Method for applying stable coating on silicone hydrogel contact lenses
WO2021163419A1 (en) 2020-02-12 2021-08-19 Tissuetech, Inc. Methods of killing or inhibiting the growth of cancer cells
EP3892259A1 (en) 2020-04-09 2021-10-13 Defymed Membranes for medical devices
WO2021204935A1 (en) 2020-04-09 2021-10-14 Defymed Membranes for medical devices
US11266772B2 (en) 2012-06-13 2022-03-08 Exthera Medical Corporation Use of heparin and carbohydrates to treat cancer
EP4032560A1 (en) 2021-01-25 2022-07-27 Centre National pour la Recherche Scientifique Implantable material in contact with blood and uses thereof
US11642412B2 (en) 2012-09-13 2023-05-09 W. L. Gore & Associates, Inc. Polytetrafluoroethylene co-polymer emulsions
US11844895B2 (en) 2014-04-24 2023-12-19 Exthera Medical Corporation Method for removing bacteria from blood using high flow rate
US11911551B2 (en) 2016-03-02 2024-02-27 Exthera Medical Corporation Method for treating drug intoxication
US12090261B2 (en) 2019-05-16 2024-09-17 Exthera Medical Corporation Method for modulating endothelial glycocalyx structure

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4521564A (en) * 1984-02-10 1985-06-04 Warner-Lambert Company Covalent bonded antithrombogenic polyurethane material
US4600652A (en) * 1985-04-01 1986-07-15 Warner-Lambert Company Permanently bonded antithrombogenic polyurethane surface
CH665954A5 (fr) * 1985-07-08 1988-06-30 Battelle Memorial Institute Substrat dont la surface presente une activite antithrombogenique.
DE3639561A1 (de) * 1986-11-20 1988-06-01 Baumann Hanno Verfahren zur herstellung von nicht-thrombogenen substraten
GB8713662D0 (en) * 1987-06-11 1987-07-15 Skandigen Ab Hyaluronic acid derivatives
US6174999B1 (en) 1987-09-18 2001-01-16 Genzyme Corporation Water insoluble derivatives of polyanionic polysaccharides
US6610669B1 (en) 1987-09-18 2003-08-26 Genzyme Corporation Water insoluble derivatives of polyanionic polysaccharides
US5527893A (en) * 1987-09-18 1996-06-18 Genzyme Corporation Water insoluble derivatives of polyanionic polysaccharides
JPH0221875A (ja) * 1988-07-11 1990-01-24 Terumo Corp 医療用材料ならびに医療用器具
NL9001387A (nl) * 1990-06-19 1992-01-16 Holland Biomaterials Group B V Werkwijze ter modificering van de eigenschappen van een substraatoppervlak door kovalente koppeling van een verbinding aan het oppervlak alsmede membraan gemodificeerd volgens de werkwijze.
DE69125828T2 (de) * 1991-05-21 1997-07-31 Hewlett Packard Gmbh Verfahren zur Vorbehandlung der Oberfläche eines medizinischen Artikels
US6743878B2 (en) 1991-07-05 2004-06-01 Biocompatibles Uk Limited Polymeric surface coatings
FR2682388B1 (fr) * 1991-10-10 1995-06-09 Pasteur Merieux Serums Vacc Procede de preparation d'un oligoside par depolymerisation d'un polyoside issu d'un agent pathogene, oligoside ainsi obtenu et son utilisation notamment comme agent vaccinal.
CA2154166A1 (en) * 1992-11-19 1994-05-26 Roger E. Marchant Nonthrombogenic implant surfaces
JPH09501044A (ja) * 1993-05-14 1997-02-04 ジ・アップジョン・カンパニー ＵＤＰ−ＧＡＬＮＡｃ：ポリペプチド、Ｎ−アセチルガラクトサミニルトランスフェラーゼをコードするクローン化されたＤＮＡ
NO931809L (no) * 1993-05-19 1994-11-21 Norsk Hydro As Hemofilter
US6294202B1 (en) 1994-10-06 2001-09-25 Genzyme Corporation Compositions containing polyanionic polysaccharides and hydrophobic bioabsorbable polymers
SE503711C2 (sv) * 1994-12-14 1996-08-12 Medicarb Ab Flerstegsförfarande för beläggning av en intraokulär lins
AU704047B2 (en) * 1995-02-07 1999-04-15 Fidia Advanced Biopolymers S.R.L. Process for the coating of objects with hyaluronic acid, derivatives thereof, and semisynthetic polymers
US5910570A (en) * 1995-11-13 1999-06-08 Pharmacia & Upjohn Company Cloned DNA encoding a UDP-GalNAc: polypeptide N-acetylgalactosaminy-ltransferase
US6051272A (en) * 1996-03-15 2000-04-18 The Board Of Trustees Of The University Of Illinois Method for synthesizing organoapatites on to surgical metal alloys
GB9624130D0 (en) 1996-11-20 1997-01-08 Biocompatibles Ltd Biocompatible compositions
US6096726A (en) 1998-03-11 2000-08-01 Surface Solutions Laboratories Incorporated Multicomponent complex for use with substrate
NO984143L (no) * 1998-09-09 2000-03-10 Norsk Hydro As Ny prosess for å fremstille overflatemodifiserende stoffer
US20050002986A1 (en) * 2000-05-12 2005-01-06 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
US6509104B2 (en) 2000-12-05 2003-01-21 Michigan Biotechnology Institute Antithrombogenic polymer coating
TW200307734A (en) 2002-03-20 2003-12-16 Michigan Biotech Inst Conductive polymer-based material
US6767405B2 (en) 2002-07-10 2004-07-27 Carmeda Ab Apparatus and process for coating articles
CA2604696C (en) 2005-04-15 2015-03-24 Interface Biologics, Inc. Polymer-biologically active agent complexes for localized delivery of said biologically active agent
US20120310210A1 (en) 2011-03-04 2012-12-06 Campbell Carey V Eluting medical devices
US9415193B2 (en) 2011-03-04 2016-08-16 W. L. Gore & Associates, Inc. Eluting medical devices
US9644040B2 (en) 2013-03-14 2017-05-09 Anacoti Ltd. Hyaluronic acid derivatives
US10569063B2 (en) 2014-10-03 2020-02-25 W. L. Gore & Associates, Inc. Removable covers for drug eluting medical devices
US10561766B2 (en) 2015-09-15 2020-02-18 W. L. Gore & Associates, Inc. Drug composition and coating
CN112807480B (zh) * 2018-08-20 2022-08-09 稳得希林(杭州)生物科技有限公司 多糖基组织粘合医用胶及其应用
IL292335A (en) * 2020-01-15 2022-06-01 Icoat Medical Ab Polyethylene glycol lipids

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2016962A (en) * 1932-09-27 1935-10-08 Du Pont Process for producing glucamines and related products
US2918462A (en) * 1956-01-20 1959-12-22 Ciba Pharm Prod Inc Process for the preparation of amino-aldehydes
US3673612A (en) * 1970-08-28 1972-07-04 Massachusetts Inst Technology Non-thrombogenic materials and methods for their preparation
SE365710B (enExample) * 1970-10-05 1974-04-01 Aminkemi Ab
US3826678A (en) * 1972-06-06 1974-07-30 Atomic Energy Commission Method for preparation of biocompatible and biofunctional materials and product thereof
FR2250795A1 (en) * 1973-11-12 1975-06-06 Univ Washington Heparinised polymer article for counter-acting blood-clot formation - prepd by reacting bromo-cyanide with hydrophilic polymer before reaction with heparin
US3947352A (en) * 1974-05-31 1976-03-30 Pedro Cuatrecasas Polysaccharide matrices for use as adsorbents in affinity chromatography techniques
FR2309245A1 (fr) * 1975-03-20 1976-11-26 Aminkemi Ab Article medical non-thrombogene et sa preparation
GB2041377A (en) * 1979-01-22 1980-09-10 Woodroof Lab Inc Bio Compatible and Blood Compatible Materials and Methods
US4301067A (en) * 1979-06-05 1981-11-17 Kureha Kagaku Kogyo Kabushiki Kaisha Chitin containing poly-ion complex
US4329383A (en) * 1979-07-24 1982-05-11 Nippon Zeon Co., Ltd. Non-thrombogenic material comprising substrate which has been reacted with heparin
US4424346A (en) * 1981-06-04 1984-01-03 Canadian Patents And Development Ltd. Derivatives of chitins, chitosans and other polysaccharides

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8200751L (sv) * 1982-02-09 1983-08-10 Olle Larm Forfarande for kovalent koppling for framstellning av konjugat och hervid erhallna produkter

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2016962A (en) * 1932-09-27 1935-10-08 Du Pont Process for producing glucamines and related products
US2918462A (en) * 1956-01-20 1959-12-22 Ciba Pharm Prod Inc Process for the preparation of amino-aldehydes
US3673612A (en) * 1970-08-28 1972-07-04 Massachusetts Inst Technology Non-thrombogenic materials and methods for their preparation
SE365710B (enExample) * 1970-10-05 1974-04-01 Aminkemi Ab
US3826678A (en) * 1972-06-06 1974-07-30 Atomic Energy Commission Method for preparation of biocompatible and biofunctional materials and product thereof
FR2250795A1 (en) * 1973-11-12 1975-06-06 Univ Washington Heparinised polymer article for counter-acting blood-clot formation - prepd by reacting bromo-cyanide with hydrophilic polymer before reaction with heparin
US3947352A (en) * 1974-05-31 1976-03-30 Pedro Cuatrecasas Polysaccharide matrices for use as adsorbents in affinity chromatography techniques
FR2309245A1 (fr) * 1975-03-20 1976-11-26 Aminkemi Ab Article medical non-thrombogene et sa preparation
SE400173B (sv) * 1975-03-20 1978-03-20 Aminkemi Ab Forfarande vid stabilisering av en hepariniserad yta innehallande vid blodkontakt utlosbart heparin
US4118485A (en) * 1975-03-20 1978-10-03 Aminkemi Aktiebolag Non-thrombogenic medical article and a method for its preparation
GB2041377A (en) * 1979-01-22 1980-09-10 Woodroof Lab Inc Bio Compatible and Blood Compatible Materials and Methods
US4301067A (en) * 1979-06-05 1981-11-17 Kureha Kagaku Kogyo Kabushiki Kaisha Chitin containing poly-ion complex
US4329383A (en) * 1979-07-24 1982-05-11 Nippon Zeon Co., Ltd. Non-thrombogenic material comprising substrate which has been reacted with heparin
US4424346A (en) * 1981-06-04 1984-01-03 Canadian Patents And Development Ltd. Derivatives of chitins, chitosans and other polysaccharides

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Biochemistry, vol. 15, No. 18, pp. 3932 3942, Shively et al. *
Biochemistry, vol. 15, No. 18, pp. 3932-3942, Shively et al.
J. Appl. Physiol. 29(5): 723 730, 1970. *
J. Appl. Physiol. 29(5): 723-730, 1970.

Cited By (276)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4810784A (en) * 1982-02-09 1989-03-07 Olle Larm Process for covalent coupling for the production of conjugates, and products hereby obtained
US4830852A (en) * 1984-12-20 1989-05-16 Merck & Co Inc. Covalently-modified neutral bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins and methods of preparing such polysaccharides and conjugates
US4772419A (en) * 1985-03-01 1988-09-20 Pharmacia Ab Shaped article and processes for its preparation
US5202431A (en) * 1985-07-08 1993-04-13 Fidia, S.P.A. Partial esters of hyaluronic acid
US4851521A (en) * 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
US5336767A (en) * 1985-07-08 1994-08-09 Fidia, S.P.A. Total or partial esters of hyaluronic acid
US5001062A (en) * 1986-05-27 1991-03-19 Camurus Ab Antithrombogenic article containing lysozyme and heparin adsorbed on a substrate
US4745180A (en) * 1986-06-27 1988-05-17 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using heparin fragments
US5262451A (en) * 1988-06-08 1993-11-16 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5342693A (en) * 1988-06-08 1994-08-30 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coating and methods of manufacture
US5338770A (en) * 1988-06-08 1994-08-16 Cardiopulmonics, Inc. Gas permeable thrombo-resistant coatings and methods of manufacture
US5100668A (en) * 1988-06-14 1992-03-31 Massachusetts Institute Of Technology Controlled release systems containing heparin and growth factors
US20060149353A1 (en) * 1988-10-04 2006-07-06 Schatz Richard A Expandable intraluminal graft
US20030195617A1 (en) * 1988-10-04 2003-10-16 Cordis Corporation Expandable intraluminal graft
US5213898A (en) * 1989-10-12 1993-05-25 Norsk Hydro A.S. Process for the preparation of surface modified solid substrates
US5310881A (en) * 1990-03-30 1994-05-10 Seikagaku Corporation Glycosaminoglycan-modified protein
US5541305A (en) * 1991-01-16 1996-07-30 Toyo Boseki Kabushiki Kaisha Composition compatible with blood
US5529986A (en) * 1991-09-26 1996-06-25 Corline Systems Ab Conjugate, its preparation and use and a substrate prepared with the conjugate
US5391580A (en) * 1992-03-20 1995-02-21 Anatrace Inc. Poly(sulfone-alpha-olefin) composite permselective membrane article for use in blood oxygenation
US5344701A (en) * 1992-06-09 1994-09-06 Minnesota Mining And Manufacturing Company Porous supports having azlactone-functional surfaces
US5451453A (en) * 1992-06-09 1995-09-19 Minnesota Mining And Manufacturing Company Supports having azlactone-functional surfaces, adduct supports, and methods of preparing both
US5401410A (en) * 1992-06-12 1995-03-28 Gambro Dialysatoren Gmbh & Co. Kg Membrane and process for the production thereof
US5292514A (en) * 1992-06-24 1994-03-08 Minnesota Mining And Manufacturing Company Azlactone-functional substrates, corneal prostheses, and manufacture and use thereof
US8067022B2 (en) 1992-09-25 2011-11-29 Boston Scientific Scimed, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US5696100A (en) * 1992-12-22 1997-12-09 Glycomed Incorporated Method for controlling O-desulfation of heparin and compositions produced thereby
US5808021A (en) * 1992-12-22 1998-09-15 Glycomed Incorporated Method for controlling O-desulfation of heparin
US6997949B2 (en) 1993-04-26 2006-02-14 Medtronic, Inc. Medical device for delivering a therapeutic agent and method of preparation
US7419696B2 (en) 1993-04-26 2008-09-02 Medtronic, Inc. Medical devices for delivering a therapeutic agent and method of preparation
US7811317B2 (en) 1993-04-26 2010-10-12 Medtronic, Inc. Medical devices for delivering a therapeutic agent and method of preparation
US20080275544A1 (en) * 1993-04-26 2008-11-06 Medtronic, Inc. Medical devices for delivering a therapeutic agent and method of preparation
US20060085064A1 (en) * 1993-04-26 2006-04-20 Medtronic, Inc. Medical devices for delivering a therapeutic agent and method of preparation
US5476665A (en) * 1994-04-13 1995-12-19 Minnesota Mining And Manufacturing Company Azlactone functional particles incorporated in a membrane formed by solvent phase inversion
US5795875A (en) * 1994-05-06 1998-08-18 Glycomed Incorporated Therapeutic methods of using O-desulfated heparin derivatives
US6486140B2 (en) 1994-07-19 2002-11-26 Medicarb Ab Agents, and methods employing them, for the prevention or reduction of tissue adhesion at a wound site
RU2153877C2 (ru) * 1994-07-19 2000-08-10 Астра Актиеболаг Агент, стимулирующий регенерацию твердой ткани
RU2155592C2 (ru) * 1994-07-19 2000-09-10 Астра Актиеболаг Антиадгезионный агент
US5814407A (en) * 1994-10-28 1998-09-29 Societe Prolabo Glycosylated particle of latex or of inorganic oxide and process for the preparation thereof
US5700559A (en) * 1994-12-16 1997-12-23 Advanced Surface Technology Durable hydrophilic surface coatings
US5807636A (en) * 1994-12-16 1998-09-15 Advanced Surface Technology Durable hydrophilic surface coatings
US5837377A (en) * 1994-12-16 1998-11-17 Advanced Surface Technology, Inc. Biomedical articles with ionically bonded polyelectrolyte coatings
US5532311A (en) * 1995-02-01 1996-07-02 Minnesota Mining And Manufacturing Company Process for modifying surfaces
US8158670B2 (en) 1995-02-15 2012-04-17 Boston Scientific Scimed, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US8097642B2 (en) 1995-02-15 2012-01-17 Boston Scientific Scimed, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US6358556B1 (en) 1995-04-19 2002-03-19 Boston Scientific Corporation Drug release stent coating
US20050187611A1 (en) * 1995-04-19 2005-08-25 Boston Scientific Scimed, Inc. Drug coating with topcoat
US20060088654A1 (en) * 1995-04-19 2006-04-27 Boston Scientific Scimed, Inc. Drug release coated stent
US5837313A (en) * 1995-04-19 1998-11-17 Schneider (Usa) Inc Drug release stent coating process
US6120536A (en) * 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US20040049265A1 (en) * 1995-04-19 2004-03-11 Schneider (Usa) Inc. Drug coating with topcoat
US6620194B2 (en) 1995-04-19 2003-09-16 Boston Scientific Scimed, Inc. Drug coating with topcoat
US20020071902A1 (en) * 1995-04-19 2002-06-13 Ni Ding Drug release stent coating
US5972717A (en) * 1995-05-10 1999-10-26 The Blood Center Research Foundation, Inc. Method and kit for detecting heparin induced thrombocytopenia
US5583213A (en) * 1995-05-12 1996-12-10 Minnesota Mining And Manufacturing Company Process to activate sulfated polysaccharides
US5865814A (en) * 1995-06-07 1999-02-02 Medtronic, Inc. Blood contacting medical device and method
US5820917A (en) * 1995-06-07 1998-10-13 Medtronic, Inc. Blood-contacting medical device and method
US5679659A (en) * 1995-08-22 1997-10-21 Medtronic, Inc. Method for making heparinized biomaterials
US5672638A (en) * 1995-08-22 1997-09-30 Medtronic, Inc. Biocompatability for solid surfaces
WO1997007834A3 (en) * 1995-08-22 1997-03-27 Medtronic Inc Method for making heparinized biomaterials
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
US5767108A (en) * 1995-08-22 1998-06-16 Medtronic, Inc. Method for making improved heparinized biomaterials
US5782908A (en) * 1995-08-22 1998-07-21 Medtronic, Inc. Biocompatible medical article and method
US20050152950A1 (en) * 1995-11-13 2005-07-14 Saffran Bruce N. Method and apparatus for macromolecular delivery using a coated membrane
US6491965B1 (en) 1995-11-30 2002-12-10 Hamilton Civic Hospitals Research Development, Inc. Medical device comprising glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US6562781B1 (en) 1995-11-30 2003-05-13 Hamilton Civic Hospitals Research Development Inc. Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US7045585B2 (en) 1995-11-30 2006-05-16 Hamilton Civic Hospital Research Development Inc. Methods of coating a device using anti-thrombin heparin
US20030124705A1 (en) * 1995-11-30 2003-07-03 Berry Leslie Roy Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US20030113314A1 (en) * 1995-11-30 2003-06-19 Hamilton Civic Hospitals Res Dev., Inc. Medical device comprising glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US20030100487A1 (en) * 1995-11-30 2003-05-29 Hamilton Civic Hospitals Res Dev., Inc. Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates
US5972718A (en) * 1996-02-28 1999-10-26 The Blood Center Research Foundation Method of detecting heparin-induced thrombocytopenia
US5928916A (en) * 1996-04-25 1999-07-27 Medtronic, Inc. Ionic attachment of biomolecules with a guanidino moiety to medical device surfaces
US6033719A (en) * 1996-04-25 2000-03-07 Medtronic, Inc. Method for covalent attachment of biomolecules to surfaces of medical devices
US5821343A (en) * 1996-04-25 1998-10-13 Medtronic Inc Oxidative method for attachment of biomolecules to surfaces of medical devices
US5945319A (en) * 1996-04-25 1999-08-31 Medtronic, Inc. Periodate oxidative method for attachment of biomolecules to medical device surfaces
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US6284305B1 (en) 1996-06-13 2001-09-04 Schneider (Usa) Inc. Drug coating with topcoat
US5728420A (en) * 1996-08-09 1998-03-17 Medtronic, Inc. Oxidative method for attachment of glycoproteins to surfaces of medical devices
US5891506A (en) * 1996-08-09 1999-04-06 Medtronic, Inc. Oxidative method for attachment of glycoproteins or glycopeptides to surfaces of medical devices
US5980972A (en) * 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5843186A (en) * 1996-12-20 1998-12-01 Implemed, Inc. Intraocular lens with antimicrobial activity
US6331422B1 (en) 1997-04-03 2001-12-18 California Institute Of Technology Enzyme-mediated modification of fibrin for tissue engineering
US6607740B1 (en) 1997-04-03 2003-08-19 California Institute Of Technology Enzyme-mediated modification of fivrin for tissue engineering
US20040082513A1 (en) * 1997-04-03 2004-04-29 California Institute Of Technology Enzyme-mediated modification of fibrin for tissue engineering
US7229473B2 (en) 1997-04-18 2007-06-12 Cordis Corporation Local delivery of rapamycin for treatment of proliferative sequelae associated with PTCA procedures, including delivery using a modified stent
US7223286B2 (en) 1997-04-18 2007-05-29 Cordis Corporation Local delivery of rapamycin for treatment of proliferative sequelae associated with PTCA procedures, including delivery using a modified stent
US7217286B2 (en) 1997-04-18 2007-05-15 Cordis Corporation Local delivery of rapamycin for treatment of proliferative sequelae associated with PTCA procedures, including delivery using a modified stent
US5879697A (en) * 1997-04-30 1999-03-09 Schneider Usa Inc Drug-releasing coatings for medical devices
US6042875A (en) * 1997-04-30 2000-03-28 Schneider (Usa) Inc. Drug-releasing coatings for medical devices
US6106454A (en) * 1997-06-17 2000-08-22 Medtronic, Inc. Medical device for delivering localized radiation
US6730120B2 (en) 1997-06-17 2004-05-04 Medtronic, Inc. Medical device for delivering a therapeutic substance and method therefor
US20040111150A1 (en) * 1997-06-17 2004-06-10 Medtronic Vascular, Inc. Medical device for delivering a therapeutic substance and method therefor
US6203536B1 (en) 1997-06-17 2001-03-20 Medtronic, Inc. Medical device for delivering a therapeutic substance and method therefor
US6197289B1 (en) 1997-07-01 2001-03-06 Terumo Cardiovascular Systems Corporation Removal of biologically active agents
US6146771A (en) * 1997-07-01 2000-11-14 Terumo Cardiovascular Systems Corporation Process for modifying surfaces using the reaction product of a water-insoluble polymer and a polyalkylene imine
US5981710A (en) * 1997-07-21 1999-11-09 Baxter International, Inc. Therapeutic hemoglobin composition having isotropically increased size
US6018035A (en) * 1997-07-21 2000-01-25 Baxter International Inc. Reagents for isotropic size enhancement of a peptide, protein, nucleotide or other substrate
US6204254B1 (en) 1997-09-12 2001-03-20 Baxter International, Inc. Biocompatible surfaces and a method for their preparation
US20020150585A1 (en) * 1997-10-03 2002-10-17 Galenica Pharmaceuticals, Inc. Use of imine-forming polysaccharides as adjuvants and immunostimulants
US6960344B2 (en) 1997-10-03 2005-11-01 Galenica Pharmaceuticals, Inc. Use of imine-forming polysaccharides as adjuvants and immunostimulants
US20040220142A1 (en) * 1997-10-03 2004-11-04 Galenica Pharmaceuticals, Inc. Imine-forming polysaccharide adjuvants and immunostimulants
US7196073B2 (en) 1997-10-03 2007-03-27 Adjuvantys, Inc. Imine-forming polysaccharide adjuvants and immunostimulants
EP1980278A2 (en) 1997-12-22 2008-10-15 Boston Scientific Scimed, Inc. Drug coating with top coat
US6017741A (en) * 1997-12-31 2000-01-25 Medtronic, Inc. Periodate oxidative method for attachment and crosslinking of biomolecules to medical device surfaces
US20070087028A1 (en) * 1998-04-16 2007-04-19 Robert Falotico Intraluminal devices for the prevention and treatment of vascular disease
US6573245B1 (en) 1998-04-28 2003-06-03 Galenica Pharmaceuticals, Inc. Modified polysaccharide adjuvant-protein antigen conjugates, the preparation thereof and the use thereof
US6013099A (en) * 1998-04-29 2000-01-11 Medtronic, Inc. Medical device for delivering a water-insoluble therapeutic salt or substance
US6399144B2 (en) 1998-04-29 2002-06-04 Medtronic Inc. Medical device for delivering a therapeutic substance and method therefor
US6206914B1 (en) 1998-04-30 2001-03-27 Medtronic, Inc. Implantable system with drug-eluting cells for on-demand local drug delivery
US6894022B1 (en) 1998-08-27 2005-05-17 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20030119186A1 (en) * 1998-08-27 2003-06-26 Eidgenossische Technische Hochschule Zurich Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides
US7241730B2 (en) 1998-08-27 2007-07-10 Universitat Zurich Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides
US7601685B2 (en) 1998-08-27 2009-10-13 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20030187232A1 (en) * 1998-08-27 2003-10-02 Eidgenossische Technische Hochschule Zurich Universitat Zurich Growth factor modified protein matrices for tissue engineering
US6960452B2 (en) 1998-08-27 2005-11-01 Eidgenossische Technische Hochschule Zurich Enzyme-mediated modification of fibrin for tissue engineering: incorporation of proteins
US6340465B1 (en) 1999-04-12 2002-01-22 Edwards Lifesciences Corp. Lubricious coatings for medical devices
US6723344B2 (en) 1999-04-22 2004-04-20 Eidgenossische Technische Hochschule Controlled release of non heparin-binding growth factors from heparin-containing matrices
US6309660B1 (en) 1999-07-28 2001-10-30 Edwards Lifesciences Corp. Universal biocompatible coating platform for medical devices
WO2001037893A1 (en) * 1999-11-23 2001-05-31 Medicarb Ab Method of covalent coupling
US6653457B1 (en) * 1999-11-23 2003-11-25 Medicarb Ab Method of covalent coupling
US7300662B2 (en) 2000-05-12 2007-11-27 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
US8236048B2 (en) 2000-05-12 2012-08-07 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
US6776796B2 (en) 2000-05-12 2004-08-17 Cordis Corportation Antiinflammatory drug and delivery device
US7056550B2 (en) 2000-09-29 2006-06-06 Ethicon, Inc. - Usa Medical devices, drug coatings and methods for maintaining the drug coatings thereon
US20070276476A1 (en) * 2000-09-29 2007-11-29 Llanos Gerard H Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US20070179595A1 (en) * 2000-09-29 2007-08-02 Davila Luis A Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US20070179597A1 (en) * 2000-09-29 2007-08-02 Davila Luis A Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US8303609B2 (en) 2000-09-29 2012-11-06 Cordis Corporation Coated medical devices
US20040005470A1 (en) * 2001-02-09 2004-01-08 Edouard Koulik Heparin compositions and methods of making and using the same
US6953625B2 (en) 2001-02-09 2005-10-11 Medtronic, Inc. Heparin compositions and methods of making and using the same
US6630460B2 (en) 2001-02-09 2003-10-07 Medtronic, Inc. Heparin compositions and methods of making and using the same
US7625410B2 (en) 2001-05-02 2009-12-01 Boston Scientific Scimed, Inc. Stent device and method
US20020165608A1 (en) * 2001-05-07 2002-11-07 Llanos Gerard H. Local drug delivery devices and methods for maintaining the drug coatings thereon
US8182527B2 (en) 2001-05-07 2012-05-22 Cordis Corporation Heparin barrier coating for controlled drug release
US7261735B2 (en) 2001-05-07 2007-08-28 Cordis Corporation Local drug delivery devices and methods for maintaining the drug coatings thereon
US20040213818A1 (en) * 2001-06-05 2004-10-28 Susumu Kashiwabara Antithrombotic compositions and medical instruments containing the same
US7195640B2 (en) 2001-09-25 2007-03-27 Cordis Corporation Coated medical devices for the treatment of vulnerable plaque
US7108701B2 (en) 2001-09-28 2006-09-19 Ethicon, Inc. Drug releasing anastomosis devices and methods for treating anastomotic sites
US20030113812A1 (en) * 2001-10-02 2003-06-19 Hemperly John J. Proliferation and differentiation of stem cells using extracellular matrix and other molecules
US7247609B2 (en) 2001-12-18 2007-07-24 Universitat Zurich Growth factor modified protein matrices for tissue engineering
US8034618B2 (en) 2001-12-18 2011-10-11 Eldgenossische Technische Hochschule Zurich PTH containing cell growth matrix
US20070179093A1 (en) * 2001-12-18 2007-08-02 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20030166833A1 (en) * 2001-12-18 2003-09-04 Eidgenossische Technische Hochschule Zurich Growth factor modified protein matrices for tissue engineering
US20030161938A1 (en) * 2002-02-22 2003-08-28 Bo Johnson Composition and method for coating medical devices
US8753663B2 (en) 2002-08-26 2014-06-17 Biotegra, Inc. Drug eluting coatings for medical implants
US8357386B2 (en) 2002-08-26 2013-01-22 Biotegra, Inc. Drug eluting coatings for medical implants and methods of use
US20040037886A1 (en) * 2002-08-26 2004-02-26 Li-Chien Hsu Drug eluting coatings for medical implants
US20050191333A1 (en) * 2002-08-26 2005-09-01 Biotegra, Inc. Drug eluting coatings for medical implants and methods of use
US7438925B2 (en) 2002-08-26 2008-10-21 Biovention Holdings Ltd. Drug eluting coatings for medical implants
US20090043388A1 (en) * 2002-08-26 2009-02-12 Biovention Holdings Ltd. Drug eluting coatings for medical implants
US20040062882A1 (en) * 2002-09-30 2004-04-01 Andrea Liebmann-Vinson Cell adhesion resisting surfaces
US20050153429A1 (en) * 2002-09-30 2005-07-14 Andrea Liebmann-Vinson Cell adhesion resisting surfaces
US9468706B2 (en) 2004-03-22 2016-10-18 Abbott Cardiovascular Systems Inc. Phosphoryl choline coating compositions
EP1609494A1 (en) 2004-06-21 2005-12-28 Cordis Corporation Heparin barrier coating for controlled drug release
US20060172438A1 (en) * 2004-10-04 2006-08-03 David Milunic Methods and kits for detecting heparin/platelet factor 4 antibodies
US9383368B2 (en) 2004-10-04 2016-07-05 Akers Biosciences, Inc. Methods for detecting heparin/platelet factor 4 antibodies
US20060147443A1 (en) * 2004-12-22 2006-07-06 Kuros Biosurgery Ag Synthetic biomaterials having incorporated therein bioactive factors through enzymatically degradable linkages
US20060148704A1 (en) * 2005-01-06 2006-07-06 Kuros Biosurgery Ag Supplemented matrices for the repair of bone fractures
US8575101B2 (en) 2005-01-06 2013-11-05 Kuros Biosurgery Ag Supplemented matrices for the repair of bone fractures
US8318674B2 (en) 2005-01-06 2012-11-27 Kuros Biosurgery Ag Local treatment of bone defects
US20070010440A1 (en) * 2005-01-06 2007-01-11 Kuros Biosurgery Ag Local treatment of bone defects
US20060159650A1 (en) * 2005-01-14 2006-07-20 Bacterin, Inc. Composition and method for covalently coupling an antithrombotic substance and a hydrophilic polymer
US10188783B2 (en) 2005-12-13 2019-01-29 Exthera Medical Corporation Method for extracorporeal removal of pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US11065378B2 (en) 2005-12-13 2021-07-20 Exthera Medical Corporation Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US10688239B2 (en) 2005-12-13 2020-06-23 Exthera Medical Corporation Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US9173989B2 (en) 2005-12-13 2015-11-03 Exthera Medical Corporation Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US9764077B2 (en) 2005-12-13 2017-09-19 Exthera Medical Corporation Method for extracorporeal removal of pathogenic microbe, an inflammatory cell or an inflammatory protein from blood
US20070264301A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized biologically active entities having a high degree of biological activity following sterilization
US20090181067A1 (en) * 2006-05-12 2009-07-16 Cleek Robert L Immobilized biologically active entities having high biological activity following mechanical manipulation
US8691260B2 (en) 2006-05-12 2014-04-08 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity
US8945599B2 (en) 2006-05-12 2015-02-03 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity
US8986713B2 (en) 2006-05-12 2015-03-24 W. L. Gore & Associates, Inc. Medical device capable of being compacted and expanded having anti-thrombin III binding activity
US9399085B2 (en) 2006-05-12 2016-07-26 W. L. Gore & Associates, Inc. Immobilized biologically active entities containing heparin having high biological activity following mechanical manipulation
US20090181066A1 (en) * 2006-05-12 2009-07-16 Cleek Robert L Immobilized biologically active entities having high biological activity folowing mechanical manipulation
US9375515B2 (en) 2006-05-12 2016-06-28 W. L. Gore & Associates, Inc. Immobilized biologically active entities having high biological activity following mechanical manipulation
US8496953B2 (en) 2006-05-12 2013-07-30 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity following sterilization
US20070264302A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized biologically active entities having high biological activity following mechanical manipulation
US20100272775A1 (en) * 2006-05-12 2010-10-28 Cleek Robert L Immobilized biologically active entities having a high degree of biological activity following sterilization
US20070264308A1 (en) * 2006-05-12 2007-11-15 Cleek Robert L Immobilized Biologically Active Entities Having High Biological Activity Following Mechanical Manipulation
US9114194B2 (en) 2006-05-12 2015-08-25 W. L. Gore & Associates, Inc. Immobilized biologically active entities having high biological activity following mechanical manipulation
US8409604B2 (en) 2006-05-12 2013-04-02 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity
US8685430B1 (en) 2006-07-14 2014-04-01 Abbott Cardiovascular Systems Inc. Tailored aliphatic polyesters for stent coatings
US8343567B2 (en) 2007-04-02 2013-01-01 Ension, Inc. Method of treating the surface of a medical device with a biomolecule
US10456227B2 (en) 2007-04-02 2019-10-29 Ension Inc. Methods of surface treating tubular medical products
US20080241349A1 (en) * 2007-04-02 2008-10-02 Ension, Inc. Process for preparing a substrate coated with a biomolecule
US9693841B2 (en) 2007-04-02 2017-07-04 Ension, Inc. Surface treated staples, sutures and dental floss and methods of manufacturing the same
US8114465B2 (en) 2007-04-02 2012-02-14 Ension, Inc. Process for preparing a substrate coated with a biomolecule
US8961947B2 (en) 2007-04-13 2015-02-24 Kuros Biosurgery Ag Polymeric tissue sealant
US20080253987A1 (en) * 2007-04-13 2008-10-16 Kuros Biosurgery Ag Polymeric tissue sealant
US9180222B2 (en) 2007-04-13 2015-11-10 Kuros Biosurgery Ag Polymeric tissue sealant
US8663148B2 (en) * 2007-06-18 2014-03-04 Exthera Medical Corporation Device and method for restoration of the condition of blood
US20100249689A1 (en) * 2007-06-18 2010-09-30 Exthera Medical Llc Device and method for restoration of the condition of blood
US9669150B2 (en) 2007-06-18 2017-06-06 Exthera Medical Corporation Device and method for restoration of the condition of blood
US20090192079A1 (en) * 2007-10-09 2009-07-30 Genzyme Corporation Prolonged delivery of heparin-binding growth factors from heparin-derivatized collagen
EP2700421A1 (en) 2007-11-09 2014-02-26 Gore Enterprise Holdings, Inc. Immobilized biologically active entities having a high degree of biological activity
US8226942B2 (en) 2007-12-28 2012-07-24 Kuros Biosurgery Ag PDGF fusion proteins incorporated into fibrin foams
US20090169539A1 (en) * 2007-12-28 2009-07-02 Kuros Biosurgery Ag Pdgf fusion proteins incorporated into fibrin foams
US8992963B2 (en) 2008-09-15 2015-03-31 Carmeda Ab Immobilised biological entities
US20100074938A1 (en) * 2008-09-15 2010-03-25 Stefan Oscarson Immobilised biological entities
CN102695530B (zh) * 2009-09-17 2018-11-30 W.L.戈尔及同仁股份有限公司 新型肝素实体及其使用方法
WO2011035001A2 (en) 2009-09-17 2011-03-24 Gore Enterprise Holding, Inc. Novel heparin entities and methods of use
US8591932B2 (en) 2009-09-17 2013-11-26 W. L. Gore & Associates, Inc. Heparin entities and methods of use
US20110065085A1 (en) * 2009-09-17 2011-03-17 Roy Biran Novel heparin entities and methods of use
CN102695530A (zh) * 2009-09-17 2012-09-26 戈尔企业控股股份有限公司 新型肝素实体及其使用方法
US20110064781A1 (en) * 2009-09-17 2011-03-17 Cleek Robert L Novel heparin entities and methods of use
US10086126B2 (en) 2009-12-01 2018-10-02 Exthera Medical Corporation Methods for removing cytokines from blood with surface immobilized polysaccharides
US11123466B2 (en) 2009-12-01 2021-09-21 Exthera Medical Corporation Methods for removing cytokines from blood with surface immobilized polysaccharides
US9408962B2 (en) 2009-12-01 2016-08-09 Exthera Medical Corporation Methods for removing cytokines from blood with surface immobilized polysaccharides
US20110223229A1 (en) * 2010-03-12 2011-09-15 Robert Vestberg Immobilised biological entities
US10842880B2 (en) 2010-03-12 2020-11-24 Carmeda Ab Immobilised biological entities
WO2011110684A1 (en) 2010-03-12 2011-09-15 Carmeda Ab Immobilised biological entities
US10016512B2 (en) 2010-03-12 2018-07-10 Carmeda Ab Immobilised biological entities
US8501212B2 (en) 2010-03-12 2013-08-06 Carmeda Ab Immobilised biological entities
US9816009B2 (en) 2010-07-30 2017-11-14 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US9411171B2 (en) 2010-07-30 2016-08-09 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US9244200B2 (en) 2010-07-30 2016-01-26 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US9239409B2 (en) 2010-07-30 2016-01-19 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
US9507173B2 (en) 2010-07-30 2016-11-29 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
US8480227B2 (en) 2010-07-30 2013-07-09 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US10781340B2 (en) 2010-07-30 2020-09-22 Alcon Inc. Silicone hydrogel lenses with water-rich surfaces
US8529057B2 (en) 2010-07-30 2013-09-10 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
US9738813B2 (en) 2010-07-30 2017-08-22 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
US8944592B2 (en) 2010-07-30 2015-02-03 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
US8939577B2 (en) 2010-07-30 2015-01-27 Novartis Ag Silicone hydrogel lenses with water-rich surfaces
US10537280B2 (en) 2011-02-15 2020-01-21 Exthera Medical Corporation Device and method for removal of blood-borne pathogens, toxins and inflammatory cytokines
US9764068B2 (en) 2011-03-11 2017-09-19 W.L. Gore And Associates Inc. Immobilised biological entities
US11497838B2 (en) 2011-03-11 2022-11-15 W. L. Gore & Associates, Inc. Immobilised biological entities
EP3375462A1 (en) 2011-03-11 2018-09-19 W.L. Gore & Associates Inc. Improvements to immobilised biological entities
US9101696B2 (en) 2011-03-11 2015-08-11 W.L. Gore & Associates, Inc. Immobilised biological entities
WO2012123384A1 (en) 2011-03-11 2012-09-20 Gore Enterprise Holdings, Inc Improvements to immobilised biological entities
US9408950B2 (en) 2011-03-11 2016-08-09 W.L. Gore & Associates, Inc. Immobilised biological entities
US10736999B2 (en) 2011-03-11 2020-08-11 W.L Gore & Associates, Inc. Immobilised biological entities
US10589001B2 (en) 2011-03-16 2020-03-17 Kuros Biosurgery Ag Pharmaceutical formulation for use in spinal fusion
US9005700B2 (en) 2011-10-12 2015-04-14 Novartis Ag Method for making UV-absorbing ophthalmic lenses
US11266772B2 (en) 2012-06-13 2022-03-08 Exthera Medical Corporation Use of heparin and carbohydrates to treat cancer
EP3838293A1 (en) 2012-07-11 2021-06-23 Tissuetech, Inc. Compositions containing hc-ha/ptx3 complexes and methods of use thereof
WO2014011813A1 (en) 2012-07-11 2014-01-16 Tissuetech, Inc. Compositions containing hc-ha/ptx3 complexes and methods of use thereof
US11642412B2 (en) 2012-09-13 2023-05-09 W. L. Gore & Associates, Inc. Polytetrafluoroethylene co-polymer emulsions
US10338408B2 (en) 2012-12-17 2019-07-02 Novartis Ag Method for making improved UV-absorbing ophthalmic lenses
WO2014118382A1 (en) 2013-02-04 2014-08-07 W. L. Gore & Associates, Inc. Coating for substrate
US9272075B2 (en) 2013-02-04 2016-03-01 W.L. Gore & Associates, Inc. Coating for substrate
US10639413B2 (en) 2013-06-24 2020-05-05 Exthera Medical Corporation Blood filtration system containing mannose coated substrate
US11306346B2 (en) 2013-11-08 2022-04-19 Exthera Medical Corporation Methods for diagnosing infectious diseases using adsorption media
US10487350B2 (en) 2013-11-08 2019-11-26 Exthera Medical Corporation Methods for diagnosing infectious diseases using adsorption media
US10457974B2 (en) 2013-11-08 2019-10-29 Exthera Medical Corporation Methods for diagnosing infectious diseases using adsorption media
US9708087B2 (en) 2013-12-17 2017-07-18 Novartis Ag Silicone hydrogel lens with a crosslinked hydrophilic coating
WO2015138862A1 (en) 2014-03-13 2015-09-17 W.L Gore & Associates, Inc. (Us) Implantable medical device
US11839698B2 (en) 2014-03-13 2023-12-12 W. L. Gore & Associates, Inc. Drug composition and coating
US11844895B2 (en) 2014-04-24 2023-12-19 Exthera Medical Corporation Method for removing bacteria from blood using high flow rate
US11633358B2 (en) 2014-06-15 2023-04-25 Yeda Research And Development Co. Ltd. Surface treatment by water-soluble polymers and lipids/liposomes
US10940111B2 (en) 2014-06-15 2021-03-09 Yeda Research And Development Co. Ltd. Surface treatment by water-soluble polymers and lipids/liposomes
US12274786B2 (en) 2014-06-15 2025-04-15 Yeda Research And Development Co. Ltd. Surface treatment of contact lens and treatment of ocular discomfort by water soluble polymers and lipids/liposomes
US11883533B2 (en) 2014-06-15 2024-01-30 Yeda Research And Development Co. Ltd. Surface treatment of contact lens and treatment of ocular discomfort by water soluble polymers and lipids/liposomes
US11002884B2 (en) 2014-08-26 2021-05-11 Alcon Inc. Method for applying stable coating on silicone hydrogel contact lenses
US10857283B2 (en) 2014-09-22 2020-12-08 Exthera Medical Corporation Wearable hemoperfusion device
WO2016184872A1 (en) 2015-05-18 2016-11-24 Defymed Functionalized membranes for bioartificial organs
EP3095509A1 (en) 2015-05-18 2016-11-23 Defymed Membranes functionalized with heparin for bioartificial organs
US10449740B2 (en) 2015-12-15 2019-10-22 Novartis Ag Method for applying stable coating on silicone hydrogel contact lenses
US11911551B2 (en) 2016-03-02 2024-02-27 Exthera Medical Corporation Method for treating drug intoxication
US10786615B2 (en) 2016-03-02 2020-09-29 Exthera Medical Corporation Method for treating drug intoxication
WO2018087102A1 (en) 2016-11-08 2018-05-17 Defymed Kit for in situ delivery of a compound of interest
EP3318294A1 (en) 2016-11-08 2018-05-09 Defymed Kit for in situ delivery of a compound of interest
US11029447B2 (en) 2017-12-13 2021-06-08 Alcon Inc. Method for producing MPS-compatible water gradient contact lenses
US10830923B2 (en) 2017-12-13 2020-11-10 Alcon Inc. Method for producing MPS-compatible water gradient contact lenses
US11029446B2 (en) 2017-12-13 2021-06-08 Alcon Inc. Method for producing MPS-compatible water gradient contact lenses
US11256003B2 (en) 2017-12-13 2022-02-22 Alcon Inc. Weekly and monthly disposable water gradient contact lenses
WO2019170858A1 (en) 2018-03-09 2019-09-12 Carmeda Ab Improvements to processes for immobilising biological entities
WO2019170859A2 (en) 2018-03-09 2019-09-12 Carmeda Ab Improvements to immobilising biological entities
US12016978B2 (en) 2018-03-09 2024-06-25 Carmeda Ab Processes for immobilising biological entities
WO2020070258A1 (en) 2018-10-03 2020-04-09 Carmeda Ab Immobilised biological entities
US11850334B2 (en) 2018-10-03 2023-12-26 Carmeda Ab Immobilised biological entities
US12090261B2 (en) 2019-05-16 2024-09-17 Exthera Medical Corporation Method for modulating endothelial glycocalyx structure
WO2021163419A1 (en) 2020-02-12 2021-08-19 Tissuetech, Inc. Methods of killing or inhibiting the growth of cancer cells
WO2021204935A1 (en) 2020-04-09 2021-10-14 Defymed Membranes for medical devices
EP3892259A1 (en) 2020-04-09 2021-10-13 Defymed Membranes for medical devices
WO2022157345A1 (en) 2021-01-25 2022-07-28 Centre National Pour La Recherche Scientifique Implantable material in contact with blood and uses thereof
EP4032560A1 (en) 2021-01-25 2022-07-27 Centre National pour la Recherche Scientifique Implantable material in contact with blood and uses thereof

Also Published As

Publication number Publication date
AU562784B2 (en) 1987-06-18
JPH0370722B2 (enExample) 1991-11-08
DE3363568D1 (en) 1986-06-26
US4810784A (en) 1989-03-07
SE8200751L (sv) 1983-08-10
JPS58147404A (ja) 1983-09-02
EP0086186B1 (en) 1986-05-21
AU1441583A (en) 1984-11-15
CA1227480A (en) 1987-09-29
EP0086186A1 (en) 1983-08-17

Similar Documents

Publication Publication Date Title
US4613665A (en) Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained
Larm et al. A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue
JP4166275B2 (ja) グリコサミノグリカン―アンチトロンビンｉｉｉ／ヘパリン補因子ｉｉ結合体
EP0658112B1 (en) A conjugate comprising a straight-chained polymer having bound sulphated glucosaminoglucans such as heparin, its preparation, use and a corresponding substrate
US7045585B2 (en) Methods of coating a device using anti-thrombin heparin
US4916219A (en) Oligosaccharide heparin fragments as inhibitors of complement cascade
Maccarana et al. Mode of interaction between platelet factor 4 and heparin
AU734112C (en) Dermatan disulfate, an inhibitor of thrombin generation and complement activation
US4496550A (en) Oligosaccharides having selective anticoagulation activity
FI103050B (fi) Menetelmä N,O-sulfatoituja heparosaaneja sisältävän koostumuksen valmi stamiseksi
JPH0635512B2 (ja) 表面変性された基材およびその製法
Larsson et al. Inhibition of thrombin on surfaces coated with immobilized heparin and heparin-like polysaccharides: A crucial non-thrombogenic principle
JPH06506685A (ja) 新規な非抗凝固剤ヘパリン誘導体
AU5765399A (en) Composition comprising heparin as a non-thrombogenic surface coating agent
Linhardt et al. Low molecular weight dermatan sulfate as an antithrombotic agent structure-activity relationship studies
JPH0257180A (ja) グリコサミノグリカン分解酵素の精製法
JP2007501305A (ja) 血漿中で高度の抗血栓活性を有する多糖類誘導体
US5416198A (en) Selective sorbent removal system using polycation activated substrates
Ebert et al. Heparin/Polymers for the prevention of surface thrombosis
Schwartz Heparin: what is it? How does it work?
Joshi et al. Synthesis and evaluation of heparin immobilized “side-on” to polystyrene microspheres coated with end-group activated polyethylene oxide
Muramatsu et al. In vitro evaluation of the heparin‐coated Gyro C1E3 blood pump
Muzzarelli et al. Sulfated N-carboxymethyl chitosans as blood anticoagulants
JPH02150297A (ja) アニオン性硫酸ポリオシドの定量方法及び該方法を実施するためのボックス
CA2378225A1 (en) Glycosaminoglycan-antithrombin iii/heparin cofactor ii conjugates

Legal Events

Date Code Title Description
STCF Information on status: patent grant

Free format text: PATENTED CASE

FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12